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| | <StructureSection load='3wmv' size='340' side='right'caption='[[3wmv]], [[Resolution|resolution]] 1.05Å' scene=''> | | <StructureSection load='3wmv' size='340' side='right'caption='[[3wmv]], [[Resolution|resolution]] 1.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3wmv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mytga Mytga]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WMV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wmv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mytilus_galloprovincialis Mytilus galloprovincialis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WMV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.05Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3wmu|3wmu]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene></td></tr> |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wmv OCA], [https://pdbe.org/3wmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wmv RCSB], [https://www.ebi.ac.uk/pdbsum/3wmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wmv ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3wmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wmv OCA], [https://pdbe.org/3wmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wmv RCSB], [https://www.ebi.ac.uk/pdbsum/3wmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wmv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/LEC1_MYTGA LEC1_MYTGA] Alpha-D-galactose-binding lectin (PubMed:27187419, PubMed:23093409, PubMed:27321048). Binds D-GalNAc, but not glucose or its derivatives (PubMed:27321048). Has hemagglutinating activity towards rabbit erythrocytes (PubMed:23093409, PubMed:27321048). Agglutinates bacteria. Has bacteriostatic activity on both Gram-positive and Gram-negative bacteria including B.subtilis, S.aureus, E.coli and V.parahaemolyticus, respectively (PubMed:27187419). Has a dose-dependent cytotoxic effect on the human globotriaosylceramide (Gb3)-expressing Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (Raji) cell line (PubMed:23093409, PubMed:27321048). Has dose-dependent cytotoxic effect on another Burkitt's lymphoma (Ramos) cell line, which does not possess the EBV genome, but also expresses Gb3. Binds to Gb3 in these cells leading to phosphorylation of MEK1/2, ERK1/2, JNK and p38 kinase, activation of caspase-9/3 and to expression of p21 and tumor necrosis factor (TNF)-alpha (PubMed:26694420). No cytotoxic effect on the human chronic myelogenous leukemia (K-562) cell line, which does not express Gb3 (PubMed:23093409, PubMed:26694420). May be involved in innate immunity acting as an antibacterial or antifungal agent (PubMed:26694420, PubMed:27321048). May be a pattern recognition receptor (PRR) involved in recognition of glycans found on parasitic or symbiotic microorganisms (PubMed:27187419).<ref>PMID:23093409</ref> <ref>PMID:26694420</ref> <ref>PMID:27187419</ref> <ref>PMID:27321048</ref> |
| - | MytiLec is a lectin, isolated from bivalves, with cytotoxic activity against cancer cell lines that express globotriaosyl ceramide, Galalpha(1,4)Galbeta(1,4)Glcalpha1-Cer, on the cell surface. Functional analysis shows that the protein binds to the disaccharide melibiose, Galalpha(1,6)Glc, and the trisaccharide globotriose, Galalpha(1,4)Galbeta(1,4)Glc. Recombinant MytiLec expressed in bacteria showed the same haemagglutinating and cytotoxic activity against Burkitt's lymphoma (Raji) cells as the native form. The crystal structure has been determined to atomic resolution, in the presence and absence of ligands, showing the protein to be a member of the beta-trefoil family, but with a mode of ligand binding unique to a small group of related trefoil lectins. Each of the three pseudo-equivalent binding sites within the monomer shows ligand binding, and the protein forms a tight dimer in solution. An engineered monomer mutant lost all cytotoxic activity against Raji cells, but retained some haemagglutination activity, showing that the quaternary structure of the protein is important for its cellular effects.
| + | |
| - | | + | |
| - | Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types.,Terada D, Kawai F, Noguchi H, Unzai S, Hasan I, Fujii Y, Park SY, Ozeki Y, Tame JR Sci Rep. 2016 Jun 20;6:28344. doi: 10.1038/srep28344. PMID:27321048<ref>PMID:27321048</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 3wmv" style="background-color:#fffaf0;"></div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 22: |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mytga]] | + | [[Category: Mytilus galloprovincialis]] |
| - | [[Category: Kawai, F]] | + | [[Category: Kawai F]] |
| - | [[Category: Noguchi, H]] | + | [[Category: Noguchi H]] |
| - | [[Category: Ozeki, Y]] | + | [[Category: Ozeki Y]] |
| - | [[Category: Park, S Y]] | + | [[Category: Park S-Y]] |
| - | [[Category: Tame, J R.H]] | + | [[Category: Tame JRH]] |
| - | [[Category: Terada, D]] | + | [[Category: Terada D]] |
| - | [[Category: Unzai, S]] | + | [[Category: Unzai S]] |
| - | [[Category: Carbohydrate]]
| + | |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Sugar binding protein]]
| + | |
| Structural highlights
Function
LEC1_MYTGA Alpha-D-galactose-binding lectin (PubMed:27187419, PubMed:23093409, PubMed:27321048). Binds D-GalNAc, but not glucose or its derivatives (PubMed:27321048). Has hemagglutinating activity towards rabbit erythrocytes (PubMed:23093409, PubMed:27321048). Agglutinates bacteria. Has bacteriostatic activity on both Gram-positive and Gram-negative bacteria including B.subtilis, S.aureus, E.coli and V.parahaemolyticus, respectively (PubMed:27187419). Has a dose-dependent cytotoxic effect on the human globotriaosylceramide (Gb3)-expressing Epstein-Barr virus (EBV)-positive Burkitt's lymphoma (Raji) cell line (PubMed:23093409, PubMed:27321048). Has dose-dependent cytotoxic effect on another Burkitt's lymphoma (Ramos) cell line, which does not possess the EBV genome, but also expresses Gb3. Binds to Gb3 in these cells leading to phosphorylation of MEK1/2, ERK1/2, JNK and p38 kinase, activation of caspase-9/3 and to expression of p21 and tumor necrosis factor (TNF)-alpha (PubMed:26694420). No cytotoxic effect on the human chronic myelogenous leukemia (K-562) cell line, which does not express Gb3 (PubMed:23093409, PubMed:26694420). May be involved in innate immunity acting as an antibacterial or antifungal agent (PubMed:26694420, PubMed:27321048). May be a pattern recognition receptor (PRR) involved in recognition of glycans found on parasitic or symbiotic microorganisms (PubMed:27187419).[1] [2] [3] [4]
References
- ↑ Fujii Y, Dohmae N, Takio K, Kawsar SM, Matsumoto R, Hasan I, Koide Y, Kanaly RA, Yasumitsu H, Ogawa Y, Sugawara S, Hosono M, Nitta K, Hamako J, Matsui T, Ozeki Y. A lectin from the mussel Mytilus galloprovincialis has a highly novel primary structure and induces glycan-mediated cytotoxicity of globotriaosylceramide-expressing lymphoma cells. J Biol Chem. 2012 Dec 28;287(53):44772-83. PMID:23093409 doi:10.1074/jbc.M112.418012
- ↑ Hasan I, Sugawara S, Fujii Y, Koide Y, Terada D, Iimura N, Fujiwara T, Takahashi KG, Kojima N, Rajia S, Kawsar SM, Kanaly RA, Uchiyama H, Hosono M, Ogawa Y, Fujita H, Hamako J, Matsui T, Ozeki Y. MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt's Lymphoma Cells to Trigger Apoptosis through Multiple Pathways. Mar Drugs. 2015 Dec 14;13(12):7377-89. PMID:26694420 doi:10.3390/md13127071
- ↑ Hasan I, Gerdol M, Fujii Y, Rajia S, Koide Y, Yamamoto D, Kawsar SM, Ozeki Y. cDNA and Gene Structure of MytiLec-1, A Bacteriostatic R-Type Lectin from the Mediterranean Mussel (Mytilus galloprovincialis). Mar Drugs. 2016 May 11;14(5):92. PMID:27187419 doi:10.3390/md14050092
- ↑ Terada D, Kawai F, Noguchi H, Unzai S, Hasan I, Fujii Y, Park SY, Ozeki Y, Tame JR. Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types. Sci Rep. 2016 Jun 20;6:28344. doi: 10.1038/srep28344. PMID:27321048 doi:http://dx.doi.org/10.1038/srep28344
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